Monday, December 5, 2016

Autism spectrum disorders: New genetic cause of identified

Autism is a general term for a group of complex disorders of brain development. These disorders are characterized, in varying degrees, by difficulties in social interaction, verbal and nonverbal communication and repetitive behaviors. Diagnosis of all forms of the disorder are put under one umbrella called autism spectrum disorder or ASD. Autism appears during the early stages of brain development around 2-3 years old and affects 1 in 68 American children. Under the website for the organization, Autism Speaks, they state some factors that can increase the risk for the child. But cases of autism are complex.
In a new study published in Cell, a team of researchers led by Gaia Novarino, professor at IST Austria, has identified a new genetic cause of ASD. With her team, they were able to identify mutations in a gene called SLC7A5 in several patients born to consanguineous marriages and diagnosed with syndromic autism. This gene transports a certain type of amino acids into the brain. The researchers performed studies on mice to understand how the mutation lead to autism. They removed the gene altogether from the mice and discovered that is caused an interference with protein synthesis in neurons. As a result, the mice showed symptoms including reduced social interaction, behavior changes. The team then reintroduced the missing SLC7A5 gene into the mice and after three weeks, improvements in behavior were observed. The researchers are excited about their results. They've found a potential treatment for a form of ASD but only in mice. It would take many more years of research until this process can be performed on human patients. Prior to the study, ASDs were always thought to be irreversible conditions.  
All in all, medical research has progressed positively in the right direction. Even though there aren't cures, mechanisms are just as important pieces of information on disorders and diseases.

Sunday, December 4, 2016

Study Reveals Key Role of mRNA's 'fifth nucleotide' in Determining Sex in Fruit Flies

A team of scientists led by the University of Birmingham has shown how a common mRNA modification, N6-methyladenosine (m6A), regulates gene expression to determine the sex of fruit flies.

The function of m6A, an mRNA modification known as the 'fifth nucleotide', has long been a mystery. But a new study, published today in Nature, has revealed that m6A plays a key role in the regulation of the Sex-lethal (Sxl) gene, which controls sex determination of the fruit fly Drosophila.
Sxl is a 'switch gene', meaning that Drosophila sex is determined by whether or not Sxl protein is made. The Sxl gene is transcribed into mRNA in both males and females, but through a process called 'alternative splicing' only the female mRNA can be made into a functional protein.

Alternative splicing is a widespread mechanism of gene expression and occurs in almost all human genes, allowing the synthesis of many more proteins than would be expected from the 20,000 protein-coding genes in our genome.

The new study shows that m6A mediates this process for Sxl in Drosophila, ultimately determining whether a fly develops as male or female. The findings offer an important insight into a classic textbook example of an essential and widely studied process.

'Despite sex determination being so fundamental, nature has found many ways of determining sex,' says Dr Matthias Soller from the School of Biosciences at the University of Birmingham and lead author on the paper.

'Our study suggests that m6A-mediated adjustment of gene expression might be an ancient yet unexplored mechanism for the development of this diversity.'

The collaboration began after co-author Dr Rupert Fray's group at the University of Nottingham found that a plant enzyme required for putting the modified nucleotide into Arabidopsis mRNA interacted with the plant version of the Drosophila sex determination factor FEMALE-LETHAL(2)D.
'The revelation connecting m6A to Drosophila sex determination though came much later thanks to sensitive genetic interactions affecting the development of female flies,' Dr Soller explains.

The study also found that in addition to its role in determining the sex of somatic cells, Sxl regulation by m6A is required to initiate germline stem cell differentiation for developing eggs. Without this regulation, lack of Sxl expression in stem cells can result in the development of ovarian cancer.

'The reversible nature of the m6A methylmark adds a new layer to the regulation of gene expression now termed "epitranscriptomics" and warrants further research to establish links with human disease such as cancer,' adds Dr Irmgard Haussmann of Coventry University.

Mitochondrial Replacement Therapy Allows Birth of First Child with DNA from Three Parents

A few months ago, the first healthy child toever have DNA from three parents was born in New York to a couple from Jordan. This was due to mitochondrial replacement therapy, a controversial procedure in which nuclear DNA is removed from a donor egg cell containing healthy mitochondria, while the nuclear DNA from a potential mother with defective mitochondria is inserted into the donor cell. The donor egg cell with the mother’s nuclear DNA is then fertilized by the father’s sperm. Though this procedure is controversial because it utilizes DNA from three parents rather than two, it is necessary in the case where the mother’s mitochondria contains harmful DNA. This harmful mitochondrial DNA can be fatal to babies. The mother of the child recently born has ¼ of her mitochondria mutated, and had two children before this experiment that were both killed from Leigh Syndrome, caused by the defective mitochondria.

However, that does not mean that the experiment is 100% perfect. Often, a few of the defective mitochondria may alsobe taken out of the mother’s cell along with the nuclear DNA during a processcalled carry-over. This unhealthy mitochondria can become prevalent in the donor cell, and can outcompete the healthy mitochondria, replicating and becoming numerous enough to cause the disease in the child. Scientists believe that this is due to the speed of mitochondrial replication, as certain genes could cause some mitochondria to replicate faster than others, resulting in unhealthy mitochondria with these genes to become more prevalent than healthy mitochondria without. Scientists hope to combat this by matching mitochondrial haplotypes between the mother and donor cells so that their speed of replication would be about the same.

Though this experiment is revolutionary, the United States as well as many other countries ban the procedure. Because of this, the doctor who performed the procedure, Dr. Zhang, had to travel to Mexico along with the couple to complete the procedure legally. However, the UK may be the first country to explicitly allow this procedure, and if approved procedures may happen as early as March or April. This is extremely important because if a highly developed country allows a procedure with a high success rate, other countries may follow suit and allow couples where the mother has faulty mitochondria to have children of their own.

The Thin Gene

In the article "The Thin Gene" Abby Solomon is discussed and her genetic disorder. Solomon is 5"10 and only weighs 99 pounds. Solomon neonatal progeroid syndrome, a condition that results from damage to the FBN1 gene. This gene causes Solomon to get hungry every hour and she begins to starve if she does not eat. She dreams about food and enjoys food but she get full very quick. Even though she thinks about food all the time she still gets full very quick and still ends up consuming less calories then a normal women her age. This mutation also "mangles noses and eyes and destroys the layer of fat under the skin so that even teenagers look middle-aged. It also interferes with the body’s ability to make a hormone called asprosin, which regulates blood sugar". Dr. Chopra of Baylor college of medicine started doing research on Abby's disorder. Dr. Chopra said that this disorder is not like a normal eating disorder, this disorder causes Abby to snack a few times every hour in order to not pass out. Abby is a great opportunity for Dr. Chopra to do research on this gene and find out what causes it. As mentioned before the hormone asprosin, which is a blood circulating hormone; asprosin deficiency keeps Abby on the brink of starvation. Dr. Chopra got to thinking that if a deficiency in asprosin causes starvation in a sense then it could help people with obesity. They tested this on mice , and found that it can reverse insulin resistance and weight gain. I found all of this very interesting and I do think it could be a great break through to help people with obesity and diabetes. When asked if she wishes she was different Abby said she would not change anything about herself because this is a chance to get to find what is wrong with her and hopefully help others.


Auditory Hallucinations Linked to MicroRNA

Schizophrenia is a mental disorder that causes people to hear voices and be generally paranoid. It's characterized by delusions, hallucinations and other mental inabilities. This illness usually shows up around adolescence or early adulthood and it affects 1.1% of the population. Schizophrenia affects not only the patient but the family, friends and those around as well. Although treatment can relieve symptoms, it can not get rid of them forever. Those who suffer with schizophrenia have to deal with these symptoms for the entirety of their lives.

Using a model mouse, researchers tried to get to the bottom of these voices. The mouse they used mimicked 22q11 deletion syndrome. Those with this syndrome are missing some parts of their chromosome 22. These parts that are missing are linked to problems in the auditory thalamus and thus causing auditory hallucinations. Roughly 20-40 percent of mice with this syndrome end up developing schizophrenia. After a few tests on this mouse, researchers identified microRNAs that could cause auditory hallucinations. If treatment was targeted towards these microRNAs, these symptoms can be greatly reduced.
Being that such a small population of people suffer with schizophrenia, not much is known about treatment. This illness is so impactful and affects people so much and the closer research gets to treating it, the better.

Saturday, December 3, 2016

Biologists unlock 51.7-million-year-old Genetic Secret

Charles Darwin proposed a hypothesis "that some species with two distinct forms of flower, where male and female reproductive organs were of differing lengths, and evolved that way to promote out-crossing by insect pollinators". Darwin coined the term 'heterostyly' because of his understanding of the two forms of flower known as pins and thrums and succeeding studies aided in building the foundation of modern genetics.

Researchers at the University of East Anglia studies the genetic code of these species' to discover what makes them that way, through an event that happened about 51 million years ago. Professor Philip Gilmartin from UEA reported that they have pinpointed the supergene responsible for this phenomenon, on the S locus. Supergenes are a group of closely related genes that can typically have related functions. Researchers worked to sequence the genome of the Primula attempting to recognize the supergene responsible for the different flower morphs.

Professor Gilmartin explained that his team found more than just the supergene, they found it is distinct to only one flower form, the thrum. He also stated that studying the genetics of flower development and reproduction can expand our knowledge of pollination which is the foundation of biodiversity and food security.

During the researchers pursuit for the genes in charge of heterostyly, they managed to date the original mutation to 51.7 million years ago. When they found the S locus, they discovered it was closely related to the gene responsible for being in command of the identity on pedals on a Primula flower. This gene was duplicated and inserted into the S locus and mutated to control the position of the anther in the flower.  The team was able to date how long ago the mutation occurred because they found the duplicated gene.

Neandertal DNA May Have Helped Europeans Survive

Geneticist Luis Barrerio conducted a study in which blood was collected from 80 people of African descent and 95 people of European descent. From these blood samples, macrophages were isolated, grown, then infected with two types of bacteria. While monitoring how the macrophages reacted to the bacteria three times faster than the macrophages from those with European descent. Researchers believe this is due to the first Homo Sapiens leaving Africa and migrating to European countries where they mated with Neandertals and adapted some of the immune responses of Neandertals in order to fight off infections they had not before encountered. A second study done in France collected two hundred samples of blood from citizens of Belgium, half of whom were of African descent and half European. In this study monocytes were isolated, grown, and infected with bacteria and viruses. The two groups showed very different immune responses again, with Neandertal-like gene variants in the European group played a major role in altering their immune response.

The change in immune response that those of European descent obtained can not yet be tracked back to the specific outbreak, but it is known that Neandertal DNA helped those of European descent survive tuberculosis due to the lowered immune response. The overactive immune systems of people of African descent can provide an explanation for why African Americans are at a much greater risk for autoimmune diseases when compared to white Americans. This research shows the need for more radical diversity in genetic studies since 80% of participants in genome-wide association studies are of European descent.

UK Company Launches Online Platform to Match Workout and Diet With Genetic Profile

London-based genomics company DNAFit has launched Elevate, an online training platform that incorporates users’ genetic information to create personalized workout plans.

Elevate, which DNAFit developed with the input of Olympic track and field athlete Greg Rutherford, is based on the company’s saliva-based genetic test kit. It screens for 45 specific gene variants, which may be linked to each individual body’s ability to respond to training and nutrition, such as those identified as being linked to obesity.

The $126 (99 British pounds) test then algorithmically calculates a score for each user to determine their endurance response, and this figure is then plugged into the Elevate online platform people can access on their smartphone, tablet or laptop. Users add their weight and other vital statistics and the days they are able to train, and the app guides them through the workout with a training schedule and videos of how to perform exercises.

“The ‘best way to train’ has long been a topic of hot debate, but it is now clear that the answer to this is an individual journey that requires the consideration of a person’s lifestyle demands and biological profile,” DNAFit founder Avi Lasarow said in a statement. “Whether you’re looking to shape up, build muscle or just want to eat a little healthier, your genetics hold valuable information about the best way to do this.”

While there still isn’t a lot of firm data to support claims that specific dietary and workout plans can be optimized for each individual based on their genetics, (geneticist Dr. Eric Topol recently told MobiHealthNews that the consumer genomics landscape is still in its early days) researchers are working to figure that out.

A recent study at the University of Central Lancashire, published in the journal Biology of Sport, suggest that those who train to their possible genetic “strengths” improved their athletic performance up to three times more than those who were using a regular training program.
Geneticist Dr Keith Grimaldi, one of the authors of the study and an advisor to DNAFit, said Elevate could be a valuable tool that takes the guesswork out of trying out different training and nutritional plans.

“We know quite a lot about some genes that do affect your biochemistry and physiology. So, we add this factor into the picture,” Grimaldi said in a statement. “If you don’t know your genes, you’ll just have to guess the right training and diet regimes by trial and error, and we want to reduce this with an extra layer of personal information from the genetic point of view.”